Validation of a natural language processing algorithm using national reporting data to improve identification of anesthesia-related ADVerse evENTs: The "ADVENTURE" study.

BACKGROUND: Reporting and analysis of adverse events (AE) is associated with improved health system learning, quality outcomes, and patient safety. Manual text analysis is time-consuming, costly, and prone to human errors. We aimed to demonstrate the feasibility of novel machine learning and natural language processing (NLP) approaches for early predictions of adverse events and provide input to direct quality improvement and patient safety initiatives. METHODS: We used machine learning to analyze 9559 continuously reported AE by clinicians and healthcare systems to the French National Health accreditor (HAS) between January 1, 2009, and December 31, 2020 . We validated the labeling of 135,000 unique de-identified AE reports and determined the associations between different system's root causes and patient consequences. The model was validated by independent expert anesthesiologists. RESULTS: The machine learning (ML) and Artificial Intelligence (AI) model trained on 9559 AE datasets accurately categorized 8800 (88%) of reported AE. The three most frequent AE types were "difficult orotracheal intubation" (16.9% of AE reports), "medication error" (10.5%), and "post-induction hypotension" (6.9%). The accuracy of the AI model reached 70.9% sensitivity, 96.6% specificity for "difficult intubation", 43.2% sensitivity, and 98.9% specificity for "medication error." CONCLUSIONS: This unsupervised ML method provides an accurate, automated, AI-supported search algorithm that ranks and helps to understand complex risk patterns and has greater speed, precision, and clarity when compared to manual human data extraction. Machine learning and Natural language processing (NLP) models can effectively be used to process natural language AE reports and augment expert clinician input. This model can support clinical applications and methodological standards and used to better inform and enhance decision-making for improved risk management and patient safety. TRIAL REGISTRATION: The study was approved by the ethics committee of the French Society of Anesthesiology (IRB 00010254-2020-20) and the CNIL (CNIL: 118 58 95) and the study was registered with ClinicalTrials.gov (NCT: NCT05185479).

Under-ice observations by trawls and multi-frequency acoustics in the Central Arctic Ocean reveals abundance and composition of pelagic fauna.

The rapid ongoing changes in the Central Arctic Ocean call for baseline information on the pelagic fauna. However, sampling for motile organisms which easily escape vertically towed nets is challenging. Here, we report the species composition and catch weight of pelagic fishes and larger zooplankton from 12 trawl hauls conducted in ice covered waters in the Central Arctic Ocean beyond the continental slopes in late summer. Combined trawl catches with acoustics data revealed low amounts of fish and zooplankton from the advective influenced slope region in the Nansen Basin in the south to the ice-covered deep Amundsen Basin in the north. Both arctic and subarctic-boreal species, including the ones considered as Atlantic expatriate species were found all the way to 87.5o N. We found three fish species (Boreogadus saida, Benthosema glaciale and Reinhardtius hippoglossoides), but the catch was limited to only seven individuals. Euphausiids, amphipods and gelatinous zooplankton dominated the catch weight in the Nansen Basin in the mesopelagic communities. Euphausiids were almost absent in the Amundsen Basin with copepods, amphipods, chaetognaths and gelatinous zooplankton dominating. We postulate asymmetric conditions in the pelagic ecosystems of the western and eastern Eurasian Basin caused by ice and ocean circulation regimes.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Combinatorial, additive and dose-dependent drug-microbiome associations.

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.

Public health potential of guidelines-based dietary scores for non-communicable diseases mortality prevention: simulation study using the Preventable Risk Integrated ModEl (PRIME) model.

OBJECTIVE: Dietary indexes measure the adherence of individuals to a set of nutritional recommendations. However, the health gains associated with adherence to various dietary indexes may vary. Our objective was to compare the magnitude of estimated avoided deaths by chronic diseases obtained by improving diet quality in the French population, measured by a variety of dietary indexes. DESIGN: Simulation study based on observational data. SETTING: Weighted data from a French population-based cohort study. PARTICIPANTS: In participants from the NutriNet-Santé cohort, we computed dietary scores reflecting the adherence to various recommendations (Medi-Lite, Healthy Diet Indicator (HDI), Programme National Nutrition Santé/National Nutrition and Health Program - Guidelines Score, Diet Quality Index (DQI), Alternative Healthy Eating Index (AHEI) and the modified Food Standards Agency nutrient profiling system dietary index (FSAm-NPS DI)). Quintiles of the food groups' consumption and dietary intakes were used as input in a simulation model (Preventable Risk Integrated ModEl (PRIME)), yielding the number of delayed or avoided deaths in nutrition-related non-communicable diseases, comparing between very high or very low nutritional quality of the diet and medium nutritional quality. RESULTS: A modification of dietary intakes from medium quality to very low quality (i.e. from the middle quintile to the quintile with the lowest nutritional quality) was associated with an increased number of deaths ranging from 3485 (95 % uncertainty interval (CI) 4002, 2987) for HDI and 3379 (95 % CI 3881, 2894) for FSAm-NPS DI to 838 (95 % CI 1163, 523) for Medi-Lite. Conversely, a modification of dietary intakes from medium quality to very high quality was associated with a decrease in the number of deaths ranging from 1995 (95 % CI 1676, 2299) for Probability of Adequate Nutrient intake diet, 1986 (95 % CI 1565, 2361) for DQI-International, 1931 (95 % CI 1499, 2316) for FSAm-NPS DI and 858 (95 % CI 499, 1205) for HDI. CONCLUSIONS: Our results provide some insights as the potential impact of following various dietary guidelines to reduce mortality from nutrition-related diseases.

Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults.

Host-microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host-microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and ß-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini-Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (-0·133 ≤ Spearman's ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host-gut microbiota metabolic relationships. In particular, our results support the implication of a 'gut-kidney axis'. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed.

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

Association of diet quality and physical activity with healthy ageing in the French NutriNet-Santé cohort.

A growing number of studies have explored overall health during ageing in a holistic manner by investigating multidimensional models of healthy ageing (HA). However, little attention has been given to the role of adherence to national nutrition guidelines in that context. This study aimed to investigate the prospective association between adherence to the French nutrition guidelines and HA. The authors analysed data from 21 407 participants of the NutriNet-Santé study with a median baseline age of 55·6 years (2009-2014) and initially free of major chronic diseases. HA was defined as not developing major chronic disease, no depressive symptoms, no function-limiting pain, independence in instrumental activities of daily living, good physical, cognitive and social functioning, as well as good self-perceived health. Adherence to guidelines of the French Nutrition and Health Programme (Programme National Nutrition Santé or PNNS) was measured via the PNNS Guideline Score (PNNS-GS), using baseline data from repeated 24-h dietary records and physical activity questionnaires. After a median follow-up of 5·7 years, 46·3 % of participants met our HA criteria. Robust-error-variance Poisson regression revealed that higher PNNS-GS scores, reflecting higher adherence to nutrition recommendations (including both diet and physical activity guidelines), were associated with a higher probability to age healthily (relative riskquartile 4 v. quartile 1 = 1·17 (95 % CI 1·12, 1·22)). Supplementary analyses revealed that this association may, to a small part, be mediated by weight status. The results suggest that high adherence to the French national nutrition recommendations may be linked to better overall health throughout ageing.

The Inflammatory Potential of the Diet is Directly Associated with Incident Depressive Symptoms Among French Adults.

BACKGROUND: Low-grade chronic inflammation has been suggested to play a substantial role in the etiology of depression; however, studies on the prospective association between the inflammatory potential of the diet and depression are limited. OBJECTIVE: The aim of this study was to investigate the association between the inflammatory potential of the diet (measured using the Alternate Dietary Inflammatory Index, ADII) and incident depressive symptoms. We also tested the potential modulating effect of sex, age, BMI, and lifestyle indicators. METHODS: The study sample consisted of 26,730 participants (aged 18-86 y) from the NutriNet-Santé study. Baseline ADII was computed using repeated 24-h dietary records collected during the first 2 y of the follow-up. Incident cases of depressive symptoms were defined by a Center for Epidemiologic Studies Depression scale ≥17 for men and ≥23 for women at least once during follow-up. HR and 95% CI were estimated using multivariable Cox proportional hazards models. RESULTS: A total of 2221 incident cases of depressive symptoms were identified over a mean follow-up of 5.4 y. After accounting for a wide range of potential confounders, the highest quartile of the ADII was associated with a 15% (95% CI: 2, 31) increase in the risk of depressive symptoms compared with the lowest quartile. In the stratified analyses, associations were statistically significant only among women (HRquartile4 vs. quartile1: 1.19; 95% CI: 1.02, 1.37), middle-age adults (HRquartile4 vs. quartile1: 1.16; 95% CI: 1.00, 1.35), and participants with a BMI ≥25 (HRquartile4 vs. quartile1: 1.29; 95% CI: 1.04, 1.60). CONCLUSIONS: Overall, a proinflammatory diet was associated with a higher risk of depressive symptoms, especially among women, middle-age adults, and participants with overweight or obesity. These findings contribute to the increasing scientific evidence showing a detrimental role of the proinflammatory diet. The NutriNet-Santé study is registered at clinicaltrials.gov as NCT03335644.

Associations between usual diet and gut microbiota composition: results from the Milieu Intérieur cross-sectional study.

BACKGROUND: Diet is widely recognized as one of the main modifiable drivers of gut microbiota variability, and its influence on microbiota composition is an active area of investigation. OBJECTIVE: The present work aimed to explore the associations between usual diet and gut microbiota composition in a large sample of healthy French adults. METHODS: Gut microbiota composition was established through sequencing of the 16S rRNA gene in stool samples from 862 healthy French adults of the Milieu Intérieur study. Usual dietary consumptions were determined through the administration of a food-frequency questionnaire. The associations between dietary variables and α- and ß-diversity indexes and relative taxa abundances were tested using Spearman correlations, permutational ANOVAs, and multivariate analyses with linear models, respectively. RESULTS: Foods generally considered as healthy (raw fruits, fish) were positively associated with α-diversity, whereas food items for which a limited consumption is generally recommended (fried products, sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts) were negatively associated with α-diversity. Fruits, fried products, ready-cooked meals, and cheese contributed to shifts within microbiota composition (ß-diversity). Our results also highlighted a number of associations between various food group intakes and abundances of specific phyla, genera, and species. For instance, the consumption of cheese was negatively associated with Akkermansia muciniphila abundance. CONCLUSIONS: This large-scale population-based study supports that the usual consumption of certain food items is associated with several gut microbial features, and extends the mechanistic arguments linking Western diet to an altered microbiota composition. These results provide new insights into the understanding of complex diet-gut microbiota relations, and their implications for host health deserve further investigation because altered microbiota diversity was consistently linked to increased risk of several health outcomes. This trial was registered at clinicaltrials.gov as NCT01699893.

Prospective association between ultra-processed food consumption and incident depressive symptoms in the French NutriNet-Santé cohort.

BACKGROUND: Ultra-processed food (UPF) consumption has increased over the last decades in Westernized countries. Our objective was to investigate for the first time the association between the proportion of UPF (%UPF) in the diet and incident depressive symptoms in the NutriNet-Santé cohort. METHODS: The sample included 20,380 women and 6350 men (aged 18-86 years) without depressive symptoms at the first Center for Epidemiologic Studies Depression Scale (CES-D) measurement, using validated cut-offs (CES-D score ≥ 17 for men and ≥ 23 for women). The proportion of UPF in the diet was computed for each subject using the NOVA classification applied to dietary intakes collected by repeated 24-h records (mean = 8; SD = 2.3). The association between UPF and depressive symptoms was evaluated using multivariable Cox proportional hazards models. RESULTS: Over a mean follow-up of 5.4 years, 2221 incident cases of depressive symptoms were identified. After accounting for a wide range of potential confounders, an increased risk of depressive symptoms was observed with an increased %UPF in the diet. In the main model adjusted for sociodemographic characteristics, body mass index, and lifestyle factors, the estimated hazard ratio for a 10% increase in UPF was 1.21 (95% confidence interval = 1.15-1.27). Considering %UPF in food groups, the association was significant only for beverages and sauces or added fats. CONCLUSION: Overall, UPF consumption was positively associated with the risk of incident depressive symptoms, suggesting that accounting for this non-nutritional aspect of the diet could be important for mental health promotion.

Prospective association between adherence to the MIND diet and subjective memory complaints in the French NutriNet-Santé cohort.

OBJECTIVES: Our objective was to examine whether adherence to the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) was associated with SMC (as measured by the cognitive difficulties scale; CDS) in the NutriNet-Santé cohort. METHODS: The study sample consisted of 6011 participants aged ≥ 60 years at baseline, without SMC at the beginning. SMC were defined by a CDS score ≥ 43 (corresponding to the 4th CDS quartile) and SMC cases were participants with SMC at least once during follow-up. The MIND diet score (0-15 points) is a hybrid of the Mediterranean Diet and the Dietary Approaches to Stop Hypertension (DASH) scores, which includes ten brain healthy food groups and five unhealthy food groups. We used Cox proportional hazards models to estimate Hazard Ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Over a mean follow-up of 6 years, approximately 15% and 30% cases of SMC were identified among participants aged 60-69 and ≥ 70 years, respectively. The MIND diet score was not significantly associated with SMC in the full sample and among participants aged 60-69 years. Among participants aged ≥ 70 years, a significant inverse association was observed between adherence to the MIND diet and SMC (HRtertile 3 vs tertile 1 = 0.69, 95% CI = 0.47-0.99). This relationship was strengthened after exclusion of participants with depressive symptoms (HRtertile 2 vs tertile 1 = 0.69, 95% CI = 0.49-0.97; HRtertile 3 vs tertile 1 = 0.62, 95% CI = 0.41-0.93). CONCLUSIONS: These findings suggest that the MIND diet could help to prevent or delay SMC among older adults without depressive symptoms.

Unsaturated Fatty Acid Intakes During Midlife Are Positively Associated with Later Cognitive Function in Older Adults with Modulating Effects of Antioxidant Supplementation.

Background: Given the drastic demographic changes characterized as "population aging," the disease burden related to dementia is a major public health problem. The scientific literature documenting the link between mono- and polyunsaturated fatty acids (MUFAs, PUFAs) and cognitive function during aging is plentiful, but findings are inconsistent. Objectives: We aimed to evaluate the association between intakes of unsaturated fatty acids at midlife and cognitive performance 13 y later in French adults, and to test for a modulating effect of antioxidant supplementation. Methods: Fatty acid intakes were estimated with the use of repeated 24-h records (1994-1996) among 3362 subjects (mean ± SD age: 65.5 ± 4.6 y) of the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study, including an intervention phase (1994-2002) during which participants were randomly assigned to an "antioxidant supplementation" or placebo group. Cognitive performance was assessed at follow-up only (in 2007-2009) via a battery of 6 standardized neuropsychological tests. A global cognitive score was calculated as the sum of T-scores of the 6 tests. Multivariable-adjusted regression analyses were performed to provide regression coefficients and 95% CIs. Results: In multivariable models, total MUFAs, total PUFAs, and n-6 PUFAs (ω-6 PUFAs) were positively associated with overall cognitive functioning. n-3 PUFA (ω-3 PUFA) intakes showed positive associations among supplemented participants only (mean difference Tertile3 versus Tertile1: 1.40; 95% CI: 0.30, 2.51; P-trend = 0.01, P-interaction = 0.01). A detrimental role of arachidonic acid for cognitive functioning was only detected in the placebo group (mean difference Tertile3 versus Tertile1: -1.38; 95% CI: -2.57, -0.18; P-trend = 0.02, P-interaction = 0.07). Conclusion: Whereas higher total MUFA and n-6 PUFA intakes may be generally beneficial for maintaining cognitive health during aging, a higher consumption of n-3 fatty acids may only be beneficial among individuals with an adequate antioxidant status. These findings underline the importance of not only focusing on specific nutrients for dementia prevention, but also considering the complex interaction between consumed nutrients. This trial was registered at clinicaltrials.gov as NCT00272428.

Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Santé Prospective Cohort Study.

Importance: Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk. Objective: To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults. Design, Setting, and Participants: In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016. Main Outcomes and Measures: This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors. Results: Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96). Conclusions and Relevance: A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association.

Prospective Association between Total and Specific Dietary Polyphenol Intakes and Cardiovascular Disease Risk in the Nutrinet-Santé French Cohort.

BACKGROUND: Epidemiological and experimental evidence support a protective effect of dietary polyphenols on chronic diseases, but high quality longitudinal data are needed, including details on categories of polyphenols. Our objective was to investigate the prospective association between total and individual classes and subclasses of dietary polyphenols and the risk of major cardiovascular disease in the NutriNet-Santé cohort. METHODS: A total of 84,158 participants, who completed at least three 24 h dietary records, were included between May 2009 and June 2017. Individual polyphenols intakes were obtained by matching food consumption data from the 24 h dietary records with the Phenol-Explorer polyphenol composition database. Multivariable Cox proportional hazards models were used to characterize the associations between dietary polyphenols and the incidence of cardiovascular diseases, comparing tertile T3 vs. T1 of classes and subclasses of polyphenols. RESULTS: Over a median of 4.9 years of follow-up, 602 major cardiovascular events were diagnosed. Intakes of anthocyanins, catechins, and flavonols were strongly inversely associated with cardiovascular disease risk (anthocyanins: Hazard Ratio (HR)for a 1-point increment of 10 mg/day = 0.98 (0.96⁻0.99, p = 0.03, HRT3vs.T1 = 0.66 (0.52⁻0.83), ptrend = 0.0003; catechins: HRfor a 1-point increment of 10 mg/day = 0.98 (0.96⁻0.99), p = 0.02, HRT3vs.T1 = 0.74 (0.60⁻0.91), ptrend = 0.004; flavonols: HRfor a 1-point increment of 10 mg/day = 0.94 (0.90⁻0.99), p = 0.02, HRT3vs.T1 = 0.75 (0.61⁻0.94), ptrend = 0.006). Intakes of dihydrochalcones, proanthocyaninidins, dihydroflavonols, hydroxybenzoic acids, and stilbenes were also associated with a decrease (13%, 19%, 24%, 24%, and 27%, respectively) in cardiovascular disease risk, when comparing tertile T3 to T1. CONCLUSIONS: Higher intakes of polyphenols, especially of anthocyanins, catechins, and flavonols, were associated with a statistically significant decreased cardiovascular disease risk.

Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes.

Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

How Healthy Lifestyle Factors at Midlife Relate to Healthy Aging.

With increasing life expectancies worldwide, it is an important public health issue to identify factors that influence the quality of aging. We aimed to investigate the individual and combined roles of lifestyle factors at midlife for healthy aging (HA). We analyzed data from 2203 participants of the French ”Supplémentation en Vitamines et Minéraux Antioxydants” (SU.VI.MAX) cohort aged 45⁻60 years at baseline (1994⁻1995), and assessed the combined impact of lifestyle factors (weight, smoking status, physical activity, alcohol consumption, and diet) on HA (absence of chronic diseases and function-limiting pain, good physical and cognitive functioning, functional independence, no depressive symptoms, and good social and self-perceived health) with a five-component healthy lifestyle index (HLI). Relative risks (RR) and 95% confidence intervals (CIs) were estimated using a robust-error-variance Poisson regression. Approximately 39% of our sample aged healthily. After adjustment for potential confounders, a one-point increase in HLI was related to an 11% higher probability of HA (95% CI = 6%, 16%; p < 0.001). The proportions of HA attributable to specific factors based on the “population attributable risk” concept were 7.6%, 6.0%, 7.8%, and 16.5% for body mass index (BMI), physical activity, diet quality, and smoking status, respectively. This study highlights the importance of healthy lifestyle habits at midlife for the promotion of good overall health during aging.

Prospective association between combined healthy lifestyles and risk of depressive symptoms in the French NutriNet-Santé cohort.

BACKGROUND: Several modifiable lifestyle indicators, including diet, smoking, alcohol consumption, weight and physical activity have been associated with depression; however, their combined effect has been less studied. The aim of this study was to calculate a Healthy Lifestyle Index (HLI) composed of the 5 above-mentioned indicators and investigate its association with incident depressive symptoms. METHODS: The study sample consisted of 25,837 participants from the NutriNet-Santé study, initially free of depressive symptoms. The HLI was computed by assigning 1 point to each lifestyle indicator namely healthy diet, healthy weight, moderate or high physical activity, never smoking and low alcohol consumption. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Hazard Ratios were estimated using Cox proportional hazards models and population attributable risks (PAR) were calculated. RESULTS: A total of 2112 incident cases of depressive symptoms were identified over a mean follow-up of 5 years. After accounting for a wide range of potential confounders, a 1-point increase in the HLI was associated with a 10% (95% CI 6%; 13%) reduction in the risk of depressive symptoms. The estimated PAR representing the proportion of cases that are attributable to non-adherence to specific healthy lifestyle indicators were 8% for healthy diet, 5% for healthy weight, 5% for non-smoking and 14% for the non-adherence to a combination of healthy diet, healthy weight and non-smoking. LIMITATIONS: Some unmeasured factors related to both depression and lifestyle indicators, such as family history of depressive disorder, stressful life events, and sleep disorders might have led to potential residual confounding. CONCLUSIONS: Modifying unhealthy lifestyles, especially diet, weight and smoking, is a potential target of major interest in the prevention of depressive symptoms in adults.